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Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families
- Source :
- Diabetes, Diabetes 68, 847-857 (2019)
- Publication Year :
- 2019
- Publisher :
- American Diabetes Association, 2019.
-
Abstract
- The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes–associated genes and a novel risk gene, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6–3.02]) and for diabetes (HR 2.92 [95% CI 2.05–4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Genotype
Endocrinology, Diabetes and Metabolism
Population
030209 endocrinology & metabolism
Autoimmunity
Human leukocyte antigen
03 medical and health sciences
Islets of Langerhans
0302 clinical medicine
Risk Factors
Diabetes mellitus
Internal medicine
HLA-DQ Antigens
Internal Medicine
medicine
Genetic predisposition
Humans
Genetic Predisposition to Disease
Family history
education
Autoantibodies
Proportional Hazards Models
Type 1 diabetes
education.field_of_study
business.industry
Hazard ratio
Genetics/Genomes/Proteomics/Metabolomics
medicine.disease
030104 developmental biology
Diabetes Mellitus, Type 1
business
Subjects
Details
- Language :
- English
- ISSN :
- 1939327X and 00121797
- Volume :
- 68
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....51e5a9725743fd5e7d4f9d3eb60887c5